Selective Recognition of Folded RNA by Small Oligomers

小寡聚体选择性识别折叠 RNA

• 批准号: 8939539
• 负责人: DANIEL H APPELLA
• 金额: $ 38.42万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8939539
• 关键词: Active Sites; Adopted; Affinity; Binding; Bioavailable; Biological; Clinical Trials; Development; Disease; Disease Progression; Drug Targeting; Event; Goals; HIV; Individual; Investigation; Knowledge; Medicine; Pharmaceutical Preparations; Process; Protein Binding; Proteins; RNA; RNA Folding; RNA-Binding Proteins; Rattus; Research; Safety; Small RNA; Specificity; Structure; Viral; Work; biophysical properties; design; drug development; effective therapy; human disease; microbicide; protein function; small molecule; three dimensional structure

New drug targets are important to study to find new and more effective therapies to alleviate human disease. Currently, RNA and associated RNA-binding proteins are significantly underutilized as a potential target for drug development: most likely because there exists a lack of basic knowledge about how one should design a molecule to target these structures. In our research, we are developing a small molecule to interfere with nucleocapid protein 7, NCp7, and its association with viral HIV RNA. In order for HIV to mature properly, NCp7 must bind to HIV RNA and protect it from degradation. Interfering with this process is a strategy to halt with HIV's progression and could become a valuable new treatment for HIV infected individuals. We have continued to develop our small molecule and are we are engaged in the necessary translational work to move our molecule toward a clinical trial. Over the past year, we have determined that the molecule is orally bioavailable and not toxic to rats. Further studies on the safety of this molecule will continue along with more investigations into the mechanism of action.

研究新的药物靶点对于找到新的、更有效的治疗方法来减轻人类疾病是很重要的。目前，作为药物开发的潜在靶点，RNA和相关的RNA结合蛋白的利用严重不足：很可能是因为缺乏关于如何设计分子来针对这些结构的基本知识。在我们的研究中，我们正在开发一种小分子来干扰核衣壳蛋白7，NCp7，及其与病毒HIV RNA的关联。为了使HIV正常成熟，NCp7必须与HIV RNA结合并保护其不被降解。干预这一过程是阻止艾滋病毒进展的一种战略，并可能成为艾滋病毒感染者的一种有价值的新疗法。我们一直在继续开发我们的小分子，我们正在从事必要的翻译工作，将我们的分子推向临床试验。在过去的一年里，我们已经确定这种分子是口服生物利用的，对老鼠没有毒性。随着对作用机制的更多研究，对这种分子的安全性的进一步研究将继续进行。